The antigenicity of -lipoprotein that had been chemically altered by acetylation or arsanilation was compared with that of native beta-lipoprotein, of lymph chylomicrons, of plasma proteins with d > 1.21, and of plasma from patients with abetalipoproteinemia. Chemical alteration causes structural changes in beta-lipoprotein which render it immunologically identical with a protein that is present both in normal plasma and in plasma from patients with abetalipoproteinemia. This protein has been identified by immunoelectrophoresis as abeta -globulin which does not stain for lipid. It is presumed to be the lipid-free apoprotein of beta-lipoprotein (B protein). The findings suggest that abetalipoproteinemia is not due to inability to synthesize B protein, but might instead be due to a defect in the formation of the complete beta-lipoprotein macro-molecule.

Abetalipoproteinemia↗

PubMed1966

The nature of pre beta (very low density) lipoproteins.

Explore the source record for details and available documents.

Adolescent↗

PubMed1965

The differentiation of exogenous and endogenous hyperlipemia by paper electrophoresis.

Explore the source record for details and available documents.

Adolescent↗

PubMedDate not supplied

Results of colestipol therapy in Type II hyperlipoproteinemia.

Twenty-five patinets with well defined Type ii hyperlipoproteinemia were treated with a divided 15 g daily dose of colestipol, a bile acid sequestrant, for periods of up to 20 months. The patients were divided into 3 groups: Those with no obvious sequelae, those with arcus corneae, xanthomas, and/or xanthelasmas only, and those with atherosclerotic complications. Colestipol lowered plasma cholesterol in all 3 groups, but reduced it to normal or near-normal levels in only 9 of the 25 patients (36%). The response of plasma triglycerides was highly varible; the mean for each group was elevated by the drug. Colestipol was well-tolerated and its effect did not diminish with time. It is a useful drug in the treatment of hypercholesterolemia.

Adolescent↗

PubMedDate not supplied

Transport of 125I-albumin across normal and deendothelialized rabbit thoracic aorta in vivo.

Transmural concentration profiles of 125I-albumin in vivo were measured across the normal and balloon catheter-deendothelialized rabbit descending thoracic aorta as a function of time following intravenous injection. A tracer was injected 5 or 60 minutes after deendothelialization, and the animals were sacrificed after circulation times of 10, 30 or 60 minutes. The aorta was immediately excised and frozen flat between glass slides. Samples were serially sectioned parallel to the intimal surface in a refrigerated microtome, washed with trichloroacetic acid (TCA), and counted. Relative tissue concentration profiles of TCA-precipitable radioactivity from the media of control animals showed entry from both luminal and adventitial sides, as previously found with conscious normal rabbits, but spatial gradients at both luminal and medial-adventitial borders were less steep. Relative concentration levels in ballooned animals were 10- to 40-fold higher than in controls, and the profiles were flatter. Uptake rates at equivalent circulation times were greater in experiments initiated 60 minutes, as compared with 5 minutes, after deendothelialization, suggesting that progressive medial edema may have occurred following balloon injury. These results show that the intact endothelium is the dominant mass transfer resistance for 125I-albumin transport across the aortic wall. The data also suggest that the incomplete monolayer of platelets adherent to the subendothelium after balloon deendothelialization is not a substantial resistance to transport, as compared to that of the media, and that convection plays a more important role than diffusion for 125I-albumin transport across the deendothelialized aortic wall.

Animals↗

PubMedDate not supplied

Local variation in arterial wall permeability to low density lipoprotein in normal rabbit aorta.

Normal rabbits were injected intravenously with horseradish peroxidase (HRP) and 125I-labeled human low density lipoprotein (LDL), and the aortas were perfusion-fixed. Subsequent visualization of HRP in the aortas was produced by reaction of the tissue with diaminobenzidine and hydrogen peroxide. The luminal surface of the aortas showed many small punctate foci of brown reaction product to the HRP, which represented penetration of the HRP into the vessel wall. The foci were scattered over the luminal surface, and most of the focal areas were less than 1 mm in diameter. The concentration of LDL was up to 47 times greater in these focal areas than in surrounding noncolored regions not showing increased permeability to HRP. Small circumscribed foci of heightened permeability to LDL may predispose to the local accumulation of lipid and ultimately to the formation of atherosclerotic plaques.

Animals↗

PubMedDate not supplied

Accumulation of native and methylated low density lipoproteins by healing rabbit arterial wall.

To determine whether healing arterial wall accumulation of low density lipoproteins (LDL) is mediated by the high affinity LDL receptor, normocholesterolemic rabbits were injected with 125I-LDL, 99mTc-LDL, or the reductively methylated analogs of these compounds (125I-MeLDL, 99mTc-MeLDL), 1 month after balloon catheter deendothelialization of the abdominal aorta. If the mechanism of accumulation requires interaction with the LDL receptor, reductively methylated lipoproteins which do not bind to the receptor should not accumulate in healing arterial wall. Twenty-four hours after injection of labelled lipoproteins, each animal was injected with Evans blue dye, in order to distinguish reendothelialized from deendothelialized aorta. One hour after dye injection, the aorta was fixed, removed, divided into abdominal (ballooned) and thoracic (unballooned) regions and counted. For all lipoprotein preparations, there were three to four times as many counts in the abdominal as in the thoracic aorta. En face autoradiographs were made of the aortas that had been exposed to 125I-labelled lipoproteins. In the autoradiographs, the areas of the lowest activity corresponded to the centers of healing endothelial islands. The most intense radioactivity for both lipoproteins occurred in the region of the leading edge of the endothelial islands where active endothelial regeneration was in progress. The overall distribution of native and MeLDL accumulation was the same. The results suggest that low density lipoproteins are accumulated in areas of active endothelial regeneration by a mechanism that does not involve the high affinity LDL receptor.

Adrenal Glands↗

PubMedDate not supplied

Imaging human atherosclerosis with 99mTc-labeled low density lipoproteins.

The feasibility of localizing human atherosclerotic plaques by gamma scintillation camera external imaging with technetium-99m-labeled low density lipoproteins (99mTc-LDL) was tested in 17 patients who had atherosclerosis. Imaging demonstrated focal accumulation of radiolabel consistent with 99mTc-LDL sequestration by plaques in the carotid, iliac, or femoral vessels of four patients 8 to 21 hours after intravenous injection of the radiopharmaceutical. Focal accumulation of 99mTc-LDL also appeared in the location of coronary lesions in four patients, but this accumulation could not be distinguished with certainty from residual blood pool radioactivity. When carotid endarterectomy specimens from six patients who received 99mTc-LDL 1 day before endarterectomy were examined, the specimens had focal accumulations of radiolabel, with two to four times greater radioactivity in some regions of each specimen than in others; this occurred whether or not the lesions were detected on the gamma camera images. Lesion composition may have determined whether accumulation was quantitatively sufficient to produce an external image. Histologically, the imaged carotid specimen had abundant foam cells and macrophages and poorly organized intramural blood consistent with a plaque hemorrhage; in contrast, nonimaged endarterectomy specimens were mature, fibrocalcific plaques. We conclude that: 1) 99mTc-LDL did accumulate in human atherosclerotic plaques; 2) in some patients, the accumulation of 99mTc-LDL was sufficient for detection by gamma camera imaging; 3) the amount of LDL that accumulated appeared to depend on lesion composition; and 4) the design of new radiopharmaceuticals with reduced residual blood pool activity relative to plaque accumulation should lead to improved external imaging of atherosclerosis.

Adult↗

PubMedDate not supplied

Intravenous nitroglycerin in experimental cerebral vasospasm. A preliminary report.

Cerebral arteriospasm is a common complication of subarachnoid hemorrhage and is responsible for much of the brain damage which accompanies it. No pharmacologic agent has been found which regularly alleviates arteriospasm. We have evaluated the effect of continuous intravenous nitroglycerin infusion on the diameter of the basilar artery in dogs with cerebral vasospasm experimentally induced by subarachnoid blood injection. In 6 consecutive dogs, 10 minutes after beginning intravenous nitroglycerin at 100 microgram/min and at other times during 120 minutes of infusion, the diameter of the basilar artery had increased from 75 +/- 2% of control value to 114 +/- 2% of control value (p less than 0.001). In all 6 dogs, the basilar artery diameter during infusion was greater than the control value prior to creating subarachnoid hemorrhage. Intravenous nitroglycerin caused only a moderate (8%) decrease in blood pressure. Further investigation of the effects of nitroglycerin on cerebral vasospasm is warranted.

Animals↗

PubMedDate not supplied

Effects of surrounding tissue on the sound spectrum of arterial bruits in vivo.

Turbulent flow distal to arterial stenoses producers bruits with a characteristic sound spectrum, analysis of which has permitted accurate non-invasive assessment of the residual lumen diameter of the stenosis in the case of the human carotid artery. In contrast, investigators working with in vitro elastic models of arteries or with excised vessels have reported finding mainly resonant spectra of bruits recorded distal to stenoses. We have studied the effects of turbulent flow on the sound spectrum produced at the arterial wall and the influence of surrounding tissue on this spectrum. Aortic, carotid, and femoral stenoses were produced in dogs by external banding of the arteries with 5mm wide Teflon bands. Recordings of bruits made directly on the vessel wall had a sound spectrum made up of 2 components, one due to turbulent flow, and the second to a superimposed resonant spectrum from arterial wall vibration. This was true of 3 kinds of vessels studied. The effects of surrounding tissue on the sound spectrum of arterial bruits was shown by comparing the spectra o bruits recorded directly on the vessel wall, on the freshly closed wound and on the healed wound. The sound properties of the artery in situ are very different from those of exposed or excised vessels or elastic tubes. Although intravascular turbulence may be accurately appreciated at the skin surface, arterial wall resonance in the intact animal is extensively damped by the normal coupling of the artery to its surrounding tissue.

Animals↗

PubMedDate not supplied

Cerebral blood flow and intracranial pressure in the dog during intravenous infusion of nitroglycerin alone and in combination with dopamine.

Nitroglycerin, long known as a safe and effective dilator of the large coronary arteries, has recently been shown to dilate the basilar artery of the dog after experimentally induced vasospasm. In this study we have evaluated the effects of intravenous nitroglycerin on local cerebral blood flow (H2 clearance technique) and intracranial pressure (intracisternal needle monitor) in normal beagle dogs (Group 1). In each of 7 dogs, infusion of nitroglycerin at rates of 3, 5, and 10 microgram/kg/min did not change blood flow in the right and left caudate nucleus, thalamus, frontal and parietal cortex. Autoregulation of cerebral blood flow remained unimpaired and intracranial pressure remained stable during nitroglycerin infusion. The effects of a combination of intravenous nitroglycerin and dopamine on local cerebral blood flow was evaluated in another group of normal beagle dogs (Group 2). Local cerebral blood flow decreased or remained unchanged in response to intravenous infusion of dopamine at low rates, increased in response to moderate rates and again decreased in response to high infusion rates. These dopamine induced changes in blood flow occurred whether or not nitroglycerin was infused simultaneously. When the vasoconstrictor activity of dopamine was blocked by phentolamine or methysergide, local cerebral blood flow increased at moderate and high infusion rates, again whether or not nitroglycerin was infused simultaneously. Our data suggest that nitroglycerin affects mainly the extracerebral capacitance arteries while dopamine affects the smaller intraparenchymal resistance vessels. Nitroglycerin has little effect on cerebral blood flow even when used in combination with dopamine.

Animals↗

PubMedDate not supplied

The natural history of carotid artery disease.

Explore the source record for details and available documents.

Arterial Occlusive Diseases↗

PubMedDate not supplied

Simultaneous therapy with antiplatelet and anticoagulant drugs in symptomatic cardiovascular disease.

Twenty of approximately 1000 patients attending the arteriosclerosis clinic at MIT during a 13 year period were treated simultaneously with aspirin and warfarin for symptomatic atherosclerotic (19) or rheumatic (1) heart or vascular disease. The average duration of therapy was 5.8 years. Thirteen patients suffered from familial hyperlipoproteinemia; only one patient had none of the major risk factors for arteriosclerosis. Refractory symptoms were related to the central nervous system in 13, peripheral vascular system in 5 and the heart in 2. All twenty patients became asymptomatic or showed marked clinical improvement on aspirin plus warfarin therapy. While on this therapy, complications, both thrombotic and hemorrhagic, occurred in 7 of the 20 patients (graft embolus in 1, and bleeding in 6; with one death as a result of intracranial bleeding) and sudden death, probably from acute myocardial ischemia, in a further 2 patients. We conclude that when alternative therapies are impossible or have proven to be of no avail in patients suffering from the complications of advanced atherosclerosis, the simultaneous administration of aspirin and warfarin may be a therapeutic alternative, although very close and careful followup of the patients' prothrombin times and clinical status is essential.

Adult↗